Cataract is a major cause of visual impairment in the world and more than 60% of the elderly population suffers from this disorder. Age related cataracts have been thought to be a consequence of the aging process, yet the etiology of age related cataract continues to remain elusive. One of the causes may be due to loss of lens epithelial cells. Although lens epithelial cells remain capable of proliferation throughout life, with increasing age, epithelial cell density is known to decrease. Interestingly, in cataract involving the lens cortex, a significantly lower cell density was reported. Epithelial cells are involved in maintaining the physiology of the lens including transparency. Thus, lens homeostasis might be disturbed by a decrease in the epithelial cell density in older lenses resulting in cataract formation. We would like to find a specific etiology which causes damage to the lens epithelial cells. Interestingly, more than 40% of healthy humans and more than 80% of cataractous patients exhibit elevated antibody titers against crystallins suggesting that autoantigens are generated. Those antibodies might damage the lens epithelial cells. Specific lens epithelial cell damage (LECD) was observed in mice injected with lens antigens possibly by an autoimmune insult induced by the antibodies against crystallins. The autoantibodies might be raised by either endogenous autoantigens or cross-reacting antigens present in infectious microbes. Infection by microbes having homologous antigens to the lens proteins can induce the autoantibodies at higher levels which may result in death of the lens epithelial cells and development of lens opacification. Thus, we hypothesize that autoantibodies against crystallins can induce trauma to the lens epithelial cells, resulting in death of the epithelial cells which lead to cataract formation. To test this hypothesis we propose the following aims. 1) Test the hypothesis that autoantibodies against lens antigens can cause LECD in mice and in cultured lens epithelial cell; 2) To determine the basic mechanism whereby autoantibodies damage lens epithelial cell, whether complement- or cell-mediated, and whether directed against cell surface or basement membrane components; 3) To determine whether leaking indigenous lens crystallins or homologous epitopes in microbial antigens are responsible for autoantibodies; 4) Design interventions to prevent autoimmune response in laboratory animals. These studies could lead to the development of interventions to prevent age related cataract in human.